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  • 1
    In: Vaccines, MDPI AG, Vol. 10, No. 4 ( 2022-03-26), p. 516-
    Abstract: First-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in either E. coli or a recombinant baculovirus system. Subsequently, the fusion protein was mixed with adjuvant and administered to mice in a prime-booster mode. Mice (72%) produced an IgG response against both proteins (titer: 10−4–10−5) 14 days after the first booster injection, which was increased to 100% by a second booster. Comparable IgG responses were detected against the delta, gamma and omicron variants of the RBD region. Durability testing revealed IgGs beyond 90 days. In addition, cytolytic effector cell molecules were increased in lymphocytes isolated from peripheral blood. Ex vivo stimulation of T cells by nucleocapsid and RBD peptides showed antigen-specific upregulation of CD44 among the CD4+ and CD8+ T cells of vaccinated mice. No side effect was documented in the central nervous system. Cumulatively, these data represent a proof-of-principle approach alternative to existing mRNA vaccination strategies.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2703319-3
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  • 2
    In: Applied Sciences, MDPI AG, Vol. 11, No. 7 ( 2021-03-30), p. 3078-
    Abstract: The determination of the ultimate shear capacity and the identification of the corresponding load-carrying mechanisms of concrete members without shear reinforcement has been an ongoing research topic for over 100 years. Based on a full mechanical model, the Shear Crack Propagation Theory (SCPT) enables to analyze and understand the ever-changing interplay of crack propagation, evolution of stresses at the crack tip and in uncracked concrete parts, as well as the activation of shear transfer actions within the growing shear crack during the entire loading process. In this paper, selected experimental investigations for further validation of the SCPT are presented. These beam shear test results are then compared to the theoretical results emerging from the SCPT algorithm. Finally, the evolution of different shear transfer actions (e.g., aggregate interlock and dowel action) during the entire loading process is evaluated and discussed.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704225-X
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  • 3
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 9 ( 2023-09-19), p. 1398-
    Abstract: In order to successfully implement individualized patient rehabilitation and home-based rehabilitation programs, the rehabilitation process should be objectifiable, monitorable and comprehensible. For this purpose, objective measurements are required in addition to subjective measurement tools. Thus, the aim of this prospective, single-center clinical trial is the clinical validation of an objective, digital medical device (DMD) during the rehabilitation after anterior cruciate ligament reconstruction (ACLR) with regards to an internationally accepted measurement tool. Sixty-seven patients planned for primary ACLR (70:30% male–female, aged 25 years [21–32], IKDC-SKF 47 [31–60] , Tegner Activity Scale 6 [4–7], Lysholm Score 57 [42–72] ) were included and received physical therapy and the DMD after surgery. For clinical validation, combined measures of range of motion (ROM), coordination, strength and agility were assessed using the DMD in addition to patient-reported outcome measures (PROMs) at three and six months after ACLR. Significant correlations were detected for ROM (rs = 0.36–0.46, p 〈 0.025) and strength/agility via the single-leg vertical jump (rs = 0.43, p = 0.011) and side hop test (rs = 0.37, p = 0.042), as well as for coordination via the Y-Balance test (rs = 0.58, p ≤ 0.0001) regarding the IKDC-SKF at three months. Additionally, DMD test results for coordination, strength and agility (Y-Balance test (rs = 0.50, p = 0.008), side hop test (rs = 0.54, p = 0.004) and single-leg vertical jump (rs = 0.44, p = 0.018)) correlate significantly with the IKDC-SKF at six months. No adverse events related to the use of the sensor-based application were reported. These findings confirm the clinical validity of a DMD to objectively quantify knee joint function for the first time. This will have further implications for clinical and therapeutic decision making, quality control and monitoring of rehabilitation measures as well as scientific research.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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  • 4
    In: Polymers, MDPI AG, Vol. 14, No. 7 ( 2022-03-25), p. 1332-
    Abstract: Charge control substances (CCS) as additives for polymer powders are investigated to make polymer powders suitable for the electrophotographic powder deposition in powder-based additive manufacturing. The use of CCS unifies the occurring charge of a powder, which is crucial for this novel deposition method. Therefore, commercially available polymer powder is functionalized via dry coating in a shaker mixer with two different CCS and analyzed afterwards. The flowability and the degree of coverage of additives on the surface are used to evaluate the coating process. The thermal properties are analyzed by use of differential scanning calorimetry. Most important, the influence of the CCS on the powder charge is shown by measurements of the electrostatic surface potential at first and the powder deposition itself is performed and analyzed with selected formulations afterwards to show the potential of this method. Finally, tensile strength specimens are produced with the conventional deposition method in order to show the usability of the CCS for current machines.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527146-5
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  • 5
    In: Tomography, MDPI AG, Vol. 8, No. 1 ( 2021-12-23), p. 22-32
    Abstract: (1) To explore the potential impact of an AI dual-energy CT (DECT) prototype on decision making and workflows by investigating its capabilities to differentiate COVID-19 from immunotherapy-related pneumonitis. (2) Methods: From 3 April 2020 to 12 February 2021, DECT from biometrically matching patients with COVID-19, pneumonitis, and inconspicuous findings were selected from our clinical routine. Three blinded readers independently scored each pulmonary lobe analogous to CO-RADS. Inter-rater agreement was determined with an intraclass correlation coefficient (ICC). Averaged perfusion metrics per lobe (iodine uptake in mg, volume without vessels in ml, iodine concentration in mg/mL) were extracted using manual segmentation and an AI DECT prototype. A generalized linear mixed model was used to investigate metric validity and potential distinctions at equal CO-RADS scores. Multinomial regression measured the contribution “Reader”, “CO-RADS score”, and “perfusion metrics” to diagnosis. The time to diagnosis was measured for manual vs. AI segmentation. (3) Results: We included 105 patients (62 ± 13 years, mean BMI 27 ± 2). There were no significant differences between manually and AI-extracted perfusion metrics (p = 0.999). Regardless of the CO-RADS score, iodine uptake and concentration per lobe were significantly higher in COVID-19 than in pneumonitis (p 〈 0.001). In regression, iodine uptake had a greater contribution to diagnosis than CO-RADS scoring (Odds Ratio (OR) = 1.82 [95%CI 1.10–2.99] vs. OR = 0.20 [95%CI 0.14–0.29] ). The AI prototype extracted the relevant perfusion metrics significantly faster than radiologists (10 ± 1 vs. 15 ± 2 min, p 〈 0.001). (4) Conclusions: The investigated AI prototype positively impacts decision making and workflows by extracting perfusion metrics that differentiate COVID-19 from visually similar pneumonitis significantly faster than radiologists.
    Type of Medium: Online Resource
    ISSN: 2379-139X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2857000-5
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  • 6
    In: Viruses, MDPI AG, Vol. 14, No. 6 ( 2022-05-28), p. 1181-
    Abstract: SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p 〈 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients 〈 45 years of age for Alpha, Gamma, and Delta (p 〈 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 9 ( 2022-04-19), p. 4509-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 9 ( 2022-04-19), p. 4509-
    Abstract: Rising incidences and mortalities have drawn attention to Clostridioides difficile infections (CDIs) in recent years. The main virulence factors of this bacterium are the exotoxins TcdA and TcdB, which glucosylate Rho-GTPases and thereby inhibit Rho/actin-mediated processes in cells. This results in cell rounding, gut barrier disruption and characteristic clinical symptoms. So far, treatment of CDIs is limited and mainly restricted to some antibiotics, often leading to a vicious circle of antibiotic-induced disease recurrence. Here, we demonstrate the protective effect of the human antimicrobial peptide α-defensin-6 against TcdA, TcdB and the combination of both toxins in vitro and in vivo and unravel the underlying molecular mechanism. The defensin prevented toxin-mediated glucosylation of Rho-GTPases in cells and protected human cells, model epithelial barriers as well as zebrafish embryos from toxic effects. In vitro analyses revealed direct binding to TcdB in an SPR approach and the rapid formation of TcdB/α-defensin-6 complexes, as analyzed with fluorescent TcdB by time-lapse microscopy. In conclusion, the results imply that α-defensin-6 rapidly sequesters the toxin into complexes, which prevents its cytotoxic activity. These findings extend the understanding of how human peptides neutralize bacterial protein toxins and might be a starting point for the development of novel therapeutic options against CDIs.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  Information Vol. 14, No. 2 ( 2023-01-27), p. 71-
    In: Information, MDPI AG, Vol. 14, No. 2 ( 2023-01-27), p. 71-
    Abstract: Twitter, one of the most important social media platforms, has been in the headlines regularly since its acquisition by Elon Musk in October 2022. This acquisition has had a strong impact on the employees, functionality, and discourse on Twitter. So far, however, there has been no analysis that examines the perception of the acquisition by the users on the platform itself. For this purpose, in this paper, we use georeferenced Tweets from the US and classify them using a polarity-based sentiment analysis. We find that the number of Tweets about Twitter and Elon Musk has increased significantly, as have negative sentiments on the subject. Using a spatial hot spot analysis, we find distinct centres of discourse, but no clear evidence of their significant change over time. On the West Coast, however, we suspect the first signs of polarisation, which could be an important indication for the future development of discourse on Twitter.
    Type of Medium: Online Resource
    ISSN: 2078-2489
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2599790-7
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  • 9
    In: Brain Sciences, MDPI AG, Vol. 10, No. 11 ( 2020-11-20), p. 886-
    Abstract: This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratioCBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratioCBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2651993-8
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  • 10
    In: Cancers, MDPI AG, Vol. 13, No. 12 ( 2021-06-19), p. 3058-
    Abstract: Talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus, is approved for intralesional injection of unresectable stage IIIB/IVM1a melanoma. However, it is still unclear which parameter(s) predict treatment response or failure. Our study aimed at characterizing surface receptors Nectin-1 and the herpes virus entry mediator (HVEM) in addition to intracellular molecules cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) as potential bio-markers for oncolytic virus treatment. In 20 melanoma cell lines, oncolytic activity of T-VEC was correlated with the expression of Nectin-1 but not HVEM, as evaluated via flow cytometry and immunohistochemistry. Knockout using CRISPR/Cas9 technology confirmed the superior role of Nectin-1 over HVEM for entry and oncolytic activity of T-VEC. Neither cGAS nor STING as evaluated by Western Blot and immunohistochemistry correlated with T-VEC induced oncolysis. The role of these biomarkers was retrospectively analyzed for the response of 35 cutaneous melanoma metastases of 21 patients to intralesional T-VEC injection, with 21 (60.0%) of these lesions responding with complete (n = 16) or partial regression (n = 5). Nectin-1 expression in pretreatment biopsies significantly predicted treatment outcome, while the expression of HVEM, cGAS, and STING was not prognostic. Altogether, Nectin-1 served as biomarker for T-VEC-induced melanoma regression in vitro and in vivo.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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